The present invention relates to a genus of substituted oximes and hydrazones useful as antagonists of tachykinin receptors, in particular as antagonists of the neuropeptides neurokinin-1 receptor (NK.sub.1) and/or neurokinin-2 receptor (NK.sub.2) and/or neurokinin-3 receptor (NK.sub.3).
Neurokinin receptors are found in the nervous system and the circulatory system and peripheral tissues of mammals, and therefore are involved in a variety of biological processes. Neurokinin receptor antagonists are consequently expected to be useful in the treatment or prevention of various mammalian disease states, for example asthma, cough, bronchospasm, inflammatory diseases such as arthritis, central nervous system conditions such as migraine and epilepsy, nociception, depression, and various gastrointestinal disorders such as Crohn's disease.
In particular, NK.sub.1 receptors have been reported to be involved in microvascular leakage and mucus secretion, and NK.sub.2 receptors have been associated with smooth muscle contraction, making NK.sub.1 and NK.sub.2 receptor antagonists especially useful in the treatment and prevention of asthma.
Substituted oxime and hydrazone NK.sub.1 and NK.sub.2 receptor antagonists have previously been disclosed in U.S. Pat. Nos. 5,696,267, 5,688,960, and 5,789,422.